Lab Dept:

Chemistry

Test Name:

SIROLIMUS LEVEL (MAYO)

General Information

Lab Order Codes:

SIRO

Synonyms:

Rapamune; Rapamycin

CPT Codes:

80195 - Sirolimus

Test Includes:

Sirolimus is a macrolide antibiotic, isolated from Stretomyces hygroscopicus, with potent effects including suppression of T-and B-cell proliferation, and antineoplastic and antifungal activity. It inhibits the protein kinase mTOR to arrest the cell cycle; it has no effects on calcineurin and, therefore, can be used in addition to cyclosporine or tacrolimus, or as a substitute in patients intolerant to these drugs. Sirolimus is metabolized by CYP34A4, thus, blood concentrations are affected by drugs that inhibit or induce this enzyme. The pharmacokinetic interaction between sirolimus and cyclosporine or tacrolimus increases both therapeutic immunosuppression and the toxicity of these agents; lower doses are required with combined use. Adverse effects of sirolimus are generally concentration-dependent, making therapeutic drug monitoring essential.

Trough sirolimus concentrations are generally measured every 5 days. Target concentrations vary depending on concomitant therapy, time posttransplant, the desired degree of immunosuppression, and adverse effects. When given with cyclosporine or tacrolimus, the therapeutic range for sirolimus is generally between 4 ng/dL to 12 ng/dL, with minimal added benefit for concentrations >10 ng/dL. When sirolimus is given without calcineurin inhibitors, higher trough levels are needed; usually12 ng/dL to 20 ng/dL, but occasionally up to 20 ng/mL to 30 ng/mL

Logistics

Test Indications:

Useful for monitoring whole blood sirolimus concentration during therapy, particularly in individuals coadministered CYP3A4 substrates, inhibitors, or inducers. Useful for adjusting dose to optimize immunosuppression while minimizing toxicity. Useful for evaluating patient compliance

Lab Testing Sections:

Chemistry - Sendout

Referred to:

Mayo Medical Laboratories (Mayo Test: SIRO)

Phone Numbers:

MIN Lab: 612-813-6280

STP Lab: 651-220-6550

Test Availability:

Daily, 24 hours

Turnaround Time:

1 - 3 Days

Special Instructions:

Draw blood immediately before a scheduled dose.

Specimen

Specimen Type:

Whole blood

Container:

Lavender-top (EDTA) tube

Draw Volume:

3 mL (Minimum: 1 mL) blood

Processed Volume:

Same as Draw Volume

Collection:

Routine venipuncture

Special Processing:

Lab Staff: Do not centrifuge. Send specimen in original vacutainer. Store and ship at refrigerated temperatures.

Patient Preparation:

None

Sample Rejection:

Specimens other than whole blood, anticoagulants other than EDTA, mislabeled specimens and unlabeled specimens

Interpretive

Reference Range:

4 - 20 ng/mL

Note: Therapeutic range applies to trough specimen drawn immediately prior to a.m. dose. Blood drawn at other times will yield higher results.

Most individuals display optimal response to sirolimus with trough whole blood levels 4 ng/mL to 20 ng/mL. Preferred therapeutic ranges may vary by transplant type, protocol, and comedications.

Critical Values:

N/A

Limitations:

The recommended therapeutic range applies to trough specimens drawn immediately before a dose.

The test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

Methodology:

High-Performance Liquid Chromatography/Tandem mass Spectrometry (HPLC-MS/MS)

Blood samples are subjected to protein precipitation. The resulting supernatant is analyzed by liquid chromatography/tandem mass spectrometry.

The assay is specific for sirolimus; it does not cross-react with cyclosporine, cyclosporine metabolites, tacrolimus, tacrolimus metabolites, or sirolimus metabolites. Results by liquid chromatography with detection by liquid chromatography/tandem mass spectrometry are approximately 30% less than by immunoassay.

References:

Mayo Medical Laboratories November 2012
Phone: 1-800-533-1710